The cephalosporin family of antibiotics is well known and includes a number of compounds which are now routinely used in combating infectious diseases. The cephalosporins are all characterized by having a 4-membered .beta.-lactam ring system fused to a 6-membered dihydrothiazine ring system. The numerous cephalosporins known differ from one another primarily in the nature of the group attached to the 7-amino group and in the nature of the substituent in the 3-position. Most of the cephalosporins known to date possess a methyl or substituted methyl group in the 3-position. A new class of cephalosporins characterized by having a 3-hydroxy or 3-alkoxy group has recently been discovered and is the subject of co-pending U.S. Pat. application Ser. No. 310,191, filed Nov. 28, 1972.
This invention relates to the reaction of 3-hydroxy cephalosporin esters with alkylfluorosulfonates. Alkylfluorosulfonates are known to be potent alkylating agents, and their reactions with certain nucleophiles yield fluorosulfonic acid, one of the strongest acids known, see for example Ahmed et al. Chemical Communications, 1533 (1968). Amines, amides, esters, ethers, and sulfides readily react with alkylfluorosulfonates. Certain ketones can be converted to the corresponding enol which is then alkylated with alkylfluorosulfonates, see for example J. B. Press et al. Tetrahedron Letters, No. 26, 2677-2680, (1972).
It is an object of this invention to provide a fast, clean, and efficient etherification process of 3-hydroxy cephalosporin esters, utilizing an alkylfluorosulfonate as the alkylating agent.